Heterogeneous molecular background of the weak C, VS+, hrB-, HrB-phenotype in black persons

BACKGROUND: The rare Hr B - phenotype is encoded by the (C)ce s haplotype when present at the homozygous state. This haplotype contains two altered genes: a hybrid RHD-CE-D s gene segregated with a ce s allele of RHCE (733C>G and 1006G>T substitutions in Exon 5 and Exon 7 respectively). The aim of this study was to further investigate the molecular background of the (C)ce s haplotype. STUDY DESIGN AND METHODS: Twelve individuals with depressed C and/or depressed e phenotype were selected from their genomic DNA analysis showing both 733C>G and 1006G>T substitutions. Phenotypic expression of low- and high-prevalence Rh antigens was studied. Complete sequences of RHD and RHCE transcripts were analyzed when obtained. RESULTS: A new hybrid RHD-CE-D s gene (Exons 1 and 2; complete Exon 3; Exons 8, 9, and 10 from RHD; and Exons 4 through 7 from RHCE) segregated with a ce s allele, which genomic organization was almost identical to that of the classical (C)ce s haplotype, is described. The two different (C)ce s haplotypes encoded two different patterns of Rh antigen expression. Although both encoded weak e, VS, and did not produce D, V, hr B , or Hr B antigens, the new haplotype encoded a much weaker C antigen and red blood cells lacked expression of Rh42, in contrast to the classic (C)ce s haplotype. CONCLUSION: The study showed the heterogeneity of the molecular background of the weak C, VS+, hr B -, Hr B - phenotype in the black population. The screening of blood donors in this population for hr B - or Hr B - phenotype should implement the molecular characterization of Rh genes.